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Sci. STKE, 5 March 2002
Vol. 2002, Issue 122, p. tw96
[DOI: 10.1126/stke.2002.122.tw96]

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Transcription Nuclear IRS-3 Can Transactivate Genes

The members of the insulin receptor substrate (IRS) family are docking proteins that participate in transducing signals that emanate from several different receptors. Kabuta et al. studied IRS-3 and found that it localized to the nucleus and might transactivate gene expression. Overexpression of IRS-1, IRS-2, or IRS-4 in cells resulted in the localization of these proteins in the cytoplasm or at the plasma membrane, whereas IRS-3 localized to the plasma membrane and nucleus. Deletion analysis of IRS-3 revealed that a region not well conserved in the other IRS proteins was essential for nuclear targeting. These data indicate that IRS-3 may be the only IRS protein that can shuttle to the nucleus. But what is its function there? Human embryonic kidney (HEK) 293 cells were transfected with a Gal4 promoter-driving gene reporter and chimeras of the Gal4 DNA-binding domain fused to segments of IRS-3. Although neither the full-length IRS-3 nor an NH2-terminal portion of IRS-3 could drive expression from the gene reporter, a 200-amino acid COOH-terminal fragment of IRS-3 stimulated gene expression from the reporter plasmid. These data suggest that IRS-3 might not only function as a docking protein for signaling proteins in the cytoplasm, but that IRS-3 might also participate in activating gene expression.

T. Kabuta, F. Hakuno, T. Asano, S.-I. Takahashi, Insulin receptor substrate-3 functions as transcriptional activator in the nucleus. J. Biol. Chem. 277, 6846-6851 (2002). [Abstract] [Full Text]

Citation: Nuclear IRS-3 Can Transactivate Genes. Sci. STKE 2002, tw96 (2002).


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